Ethanol → N-[3-(2-Fluoro-4'-hydroxymethyl-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide

HRID 273256Notes

Reaction equation

HRID 273256 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][CH:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])[CH:5]=[CH:6][C:7]=1I.[OH:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].C(O)C>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][CH:12]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[O:11][C:10]2=[O:19])[CH:5]=[CH:6][C:7]=1[C:25]1[CH:26]=[CH:27][C:22]([CH2:21][OH:20])=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 11728568(S)-N-[3-(3-Fluoro-4-iodophenyl)-2-oxo-oxazolidin-5-ylmethyl]acetamide

Product 1

HCID 21907449N-[3-(2-Fluoro-4'-hydroxymethyl-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamideYield 94.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

A suspension of N-[3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 50 (14.0 g, 37 mmol) in toluene (120 mL) was treated with 4-(hydroxymethyl) phenylboronic acid (7.87 g, 51.8 mmol, 1.4 equiv), potassium carbonate (K2CO3, 15.32 g, 111 mmol, 3.0 equiv), ethanol (EtOH, 40 mL), and H2O (40 mL) at 25° C., and the resulting mixture was degassed three times under a steady-stream of argon at 25° C. Tetrakis(triphenylphosphine)palladium (Pd(PPh3)4, 2.14 g, 1.85 mmol, 0.05 equiv) was subsequently added to the reaction mixture, and the resulting reaction mixture was degassed three times again before being warmed to gentle reflux for 6 h. When thin layer chromatography (TLC) and HPLC showed the coupling reaction was complete, the reaction mixture was cooled to room temperature before being treated with H2O (240 mL). The resulting mixture was then stirred at room temperature for 10 min before being cooled to 0-5° C. for 1 h. The solid precipitates were collected by filtration, washed with H2O (2×100 mL) and 20% ethyl acetate (EtOAc)/hexane (2×50 mL), and dried in vacuo. The crude desired N-[3-(2-Fluoro-4′-hydroxymethyl-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 51 (12.50 g, 94% yield) was obtained as off-white solids. This material was found to be essentially pure by HPLC and 1H NMR and was directly used in the subsequent reaction without further purification. 1H NMR (300 MHz, DMSO-d6) δ 1.76 (s, 3H, COCH3), 3.35 (t, 2H, J=5.4 Hz), 3.69 (dd, 1H, J=6.4, 9.2 Hz), 4.08 (t, 1H, J=9.1 Hz), 4.46 (d, 2H, J=5.7 Hz, CH2OH), 4.68 (m, 1H), 5.16 (t, 1H, J=5.7 Hz, OH), 7.25-7.52 (m, 7H, aromatic-H), 8.18 (t, 1H, J=5.8 Hz, NHCOCH3). LCMS (ESI) m/e 359 (M+H)+.

Workup

  1. customthe resulting mixture was degassed three times under a steady-stream of argon at 25° C
  2. customthe resulting reaction mixture
  3. customwas degassed three times again
  4. temperaturebefore being warmed
  5. temperatureto gentle reflux for 6 h
  6. customthe coupling reaction
  7. temperaturebefore being cooled to 0-5° C. for 1 h
  8. customThe solid precipitates
  9. filtrationwere collected by filtration
  10. washwashed with H2O (2×100 mL) and 20% ethyl acetate (EtOAc)/hexane (2×50 mL)
  11. customdried in vacuo

Sources & evidence

ORD record
ord-e46b5a569a3a45689a912adf54b28efa
Source dataset
uspto-grants-2008_11
Patent number
US07456206B2

Reaction notes

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